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Commercial gene expression tests for prostate cancer prognosis provide paradoxical estimates of race-specific risk

By Jordan H Creed, Anders E Berglund, Robert J Rounbehler, Shivanshu Awasthi, John L Cleveland, Jong Y. Park, Kosj Yamoah, Travis A Gerke

Posted 12 Apr 2019
bioRxiv DOI: 10.1101/604058 (published DOI: 10.1158/1055-9965.EPI-19-0407)

Background: Commercial gene expression signatures of prostate cancer (PCa) prognosis were developed and validated in cohorts of predominantly European American men (EAM). Limited research exists on the value of such signatures in African American men (AAM), who have poor PCa outcomes. We explored differences in gene expression between EAM and AAM for three commercially available panels recommended by the National Comprehensive Cancer Network for PCa prognosis. Materials and Methods: 232 EAM and 95 AAM patients provided radical prostatectomy specimens. Gene expression was quantified using Nanostring for 60 genes spanning the Oncotype DX Prostate, Prolaris, and Decipher panels. A continuous expression-based risk score was approximated for each. Differential expression, intrapanel co-expression and risk by race were assessed. Results and limitations: Clinical and pathologic features were similar between AAM and EAM. Differential expression by race was observed for 48% of genes measured, though the magnitudes of expression differences were small. Co-expression patterns were more strongly preserved by race group for Oncotype DX and Decipher versus Prolaris (integrative correlations of 0.87, 0.73, and 0.62, respectively). Poorer prognosis was estimated in EAM versus AAM for Oncotype DX (p < 0.001), whereas no difference in prognosis was predicted between AAM and EAM using Prolaris or Decipher (p > 0.05). Replication of our findings directly on the commercial panels with long-term follow-up is warranted. Conclusions: Due to observed racial differences across three commercial gene expression panels for PCa prognosis, caution is warranted when applying these panels in clinical decision-making in AAM.

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